NOTES TO EDITORS
PROfound is a prospective, multi-center, randomized, open-label, Phase III trial testing the efficacy and safety of LYNPARZA 300 mg (two 150 mg tablets) twice daily versus new hormonal agents (e.g., abiraterone or enzalutamide) in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on prior treatment with new hormonal anticancer treatments and have a qualifying tumor mutation in one of 15 genes involved in the homologous recombination repair (HRR) pathway, including among them BRCA1/2, ATM and CDK12.
The trial was designed to analyze men with HRRm genes in two cohorts (BRCA 1/2 or ATM mutations and overall HRRm): the primary endpoint was in those with mutations in BRCA1/2 or ATM genes and then, if LYNPARZA (olaparib) showed clinical benefit, a formal analysis was performed of the overall trial population of men with HRRm genes (BRCA1/2, ATM, CDK12 7072彩票代理and 11 other HRRm genes; key secondary endpoint).
Results showed a statistically significant and clinically meaningful improvement with LYNPARZA in the primary endpoint of radiographic progression-free survival (rPFS), improving the time men with BRCA1/2- or ATM-mutated mCRPC lived without disease progression to a median of 7.4 months vs. 3.6 months for those treated with abiraterone or enzalutamide and reduced the risk of disease progression or death by 66% (HR 0.34 [95% CI, 0.25-0.47], p<0.0001). The trial also met the key secondary endpoint of rPFS in the overall HRRm population, where LYNPARZA reduced the risk of disease progression or death by 51% and improved rPFS to a median of 5.8 months vs. 3.5 months for those receiving abiraterone or enzalutamide (HR 0.49 [95% CI, 0.38-0.63], p<0.0001).
About Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Prostate cancer is the second-most common cancer in men. An estimated 191,930 men in the United States will be diagnosed with prostate cancer in 2020. Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone. mCRPC occurs when prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones. Approximately 10-20% of men with advanced prostate cancer will develop CRPC within five years, and at least 84% of these will have metastases at the time of CRPC diagnosis. Of men with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years. Despite an increase in the number of available therapies for men with mCRPC, five-year survival remains low.
About Homologous Recombination Repair (HRR) Gene Mutations
HRR is a DNA repair process that allows for high-fidelity, error-free repair of damaged DNA, in the form of double-strand breaks and inter-strand crosslinks (amongst others). The inability to properly repair DNA damage leads to genomic instability and contributes to cancer etiology. Deficiency in HRR leads to a compromised ability to repair damaged DNA, and is a feature of cancer cells that is a target for PARP inhibitors, such as LYNPARZA. PARP inhibitors block DNA damage repair by trapping of PARP bound to DNA single-strand breaks which leads to replication fork stalling causing their collapse and the generation of DNA double-strand breaks which in turn lead to cancer cell death.
LYNPARZA? (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumors harboring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. LYNPARZA is being tested in a range of PARP-dependent tumor types with defects and dependencies in the DDR pathway.
7072彩票代理LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad and advanced clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types.
About the AstraZeneca and Merck Strategic Oncology Collaboration
7072彩票代理In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize LYNPARZA, the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop LYNPARZA and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop LYNPARZA and selumetinib in combination with their respective PD-L1 and PD-1 medicines.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in hematology.
By harnessing the power of four scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal and Metabolism, and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit gdlvh.com 7072彩票代理and follow us on 7072彩票代理 @AstraZenecaUS.